Age-related changes of monoamine levels, turnover, and synaptosomal uptake processes have been found in the hypothalamus and striatium of C57BL/6J male mice and other mammals. Deficiencies of neural monoamines may underlie a variety of physiological and behavioral phenomena of aging. This hypothesis will be tested in relation to the onset of estrous irregularities during aging in strains of mice (C57BL/6J and BALB/c) which have different levels of brain monoamines. Studies will also be made in these strains on the effect of aging and hormonal status on synaptosomal uptake of monoamines and on monoamine levels in the hypothalamus and striatum. Autoradiographic studies will investigate if a loss of monoaminergic cells occurs (in the substantia nigra, arcuate nucleus, locus coeruleus, and the raphe) which may influence monoaminergic mechanisms. The interaction of drugs which inhibit catecholamine uptake (e.g., amphetamines, phenothiazines) will be used to further characterize the aging changes in uptake mechanisms.